Enhancement of vascular function by modulation of endogenous nitric oxide production or activity

Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds, namely L-arginine, L-lysine, physiologically acceptable salts thereof, and polypeptide precursors thereof, which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. In or in combination, other compounds, such as B.sub.6, folate, B.sub.12, or an antioxidant, which provide for short term enhancement of nitric oxide, either directly or by physiological processes may be employed.

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Claims

1. A method of improving vascular NO activity of the vascular system of a human host by enhancing endothelial NO, said method comprising:

administering orally as a dietary supplement to said host in accordance with a predetermined regimen a prophylactic dose in an amount sufficient to enhance endogenous endothelial NO, L-arginine or L-arginine hydrochloride, as other than a natural food source and in the absence of other amino acids and polypeptides as other that dietary supplements, to enhance the level of endogenous NO in the vascular system.

2. A method of improving vascular NO activity of the vascular system of a human host by enhancing endothelial NO, said method comprising:

administering orally as a dietary supplement to said host in accordance with a predetermined regimen a prophylactic dose in an amount sufficient to enhance endogenous endothelial NO, from 2-25 g of L-lysine or physiologically acceptable salts thereof as other than a natural food source and in the absence of other amino acids and polypeptides as other than dietary supplements, and any Vitamin C being present in from 250-2000 mg, to enhance the level of endogenous NO in the vascular system.

3. A method of improving vascular NO activity of the vascular system of a human host by enhancing endothelial NO, said method comprising:

administering orally as a dietary supplement to said host in accordance with a predetermined regimen a prophylactic dose in an amount sufficient to enhance endogenous endothelial NO, a mixture of L-arginine and L-lysine or their physiologically acceptable salts, as other than a natural food source and in the absence of other amino acids and polypeptides as other than dietary supplements, to enhance the level of endogenous NO in the vascular system to improve vascular function.

4. A method according to any of claims 2 and 3, wherein said dose is administered in combination with at least one antioxidant selected from the group consisting of Vitamin C, Vitamin E and carotene.

5. A method according to any of claims 2 and 3, wherein said dose is administered at a dosage in the range of 0.5 to 5 g per dose.

6. A method according to any of claims 2 and 3, wherein said dose comprises at least one of calcium, Vitamin C, Vitamin E, coenzyme Q, carotene, glutathione, an amino acid absorption enhancing compound or an antioxidant in an amount sufficient to enhance said prophylactic effect.

7. A method according to any of claims 2 and 3, wherein said dose is in the range of 0.5-10 g in combination with at least one of calcium, B.sub.6, B.sub.12, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the prophylactic effect.

8. A method according to any of claims 2 and 3, wherein said dose is administered as a tablet, capsule, or powder.

9. A method according to claims 2 and 3, wherein said dose is administered as a prepared solid food or liquid.

10. A physiologically acceptable formulation as a health bar, soft drink or cereal comprising amino acids in the range of about 3-15 g, said amino acids consisting of L-arginine or L-arginine hydrochloride, and at least one of folate, B.sub.12, B.sub.6, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the effect of said L-arginine or L-arginine hydrochloride on enhancing the amount of endothelial NO in a human host.

11. A physiologically acceptable formulation as a health bar or soft drink comprising L-lysine or its physiologically acceptable salt in the range of about 3-15 g per dosage or bar and at least one of folate, B.sub.12, B.sub.6, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the effect of said L-lysine or its physiologically acceptable salt on enhancing the amount of endothelial NO in a human host.

12. A physiologically acceptable formulation comprising as a health bar, soft drink or cereal, a mixture of L-arginine and L-lysine or their physiologically acceptable salts in the range of about 3-15 g and at least one of folate, B.sub.6, B.sub.12, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the effect of said mixture on enhancing the amount of endothelial NO in a human host.

13. A method according to claim 1, wherein said dose is administered as a formulation consisting of a health bar, soft drink or cereal comprising amino acids selected from the group consisting of L-arginine and L-arginine hydrochloride in the range of about 3-15 g and at least one of folate, B.sub.12, B.sub.6, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the effect of said L-arginine or L-arginine hydrochloride on enhancing the amount of endothelial NO in a human host.

14. A method according to claim 2, wherein said dose is administered as a formulation consisting of a health bar, soft drink or cereal comprising amino acids selected from the group consisting of L-lysine and its physiologically acceptable salts in the range of about 3-15 g and at least one of folate, B.sub.12, B.sub.6, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the effect of said L-lysine or its physiologically acceptable salt on enhancing the amount of endothelial NO in a human host.

15. A method according to claim 3, wherein said dose is administered as a formulation consisting of a health bar, soft drink or cereal comprising a mixture of L-arginine and L-lysine or their physiologically acceptable salts in the range of bout 3-15 g and at least one of folate, B.sub.12, B.sub.6, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the effect of said mixture of L-arginine and L-lysine and their physiologically acceptable salts on enhancing the amount of endothelial NO in a human host.

16. A method according to any of claims 13 to 15, wherein said formulation is a health bar.

17. A method according to claim 1, wherein said dose is administered in combination with at least one antioxidant selected from the group consisting of Vitamin C, Vitamin E and carotene.

18. A method according to claim 1, wherein said dose is administered at a dosage in the range of 3-15 g per dose.

19. A method according to claim 1, wherein said dose comprises at least one of calcium, Vitamin C, Vitamin E, coenzyme Q, carotene, glutathione, an amino acid absorption enhancing compound or an antioxidant in an amount sufficient to enhance said prophylactic effect.

20. A method according to claim 1, wherein said dose is in the range of 0.5-10 g in combination with at least one of calcium, B.sub.6, B.sub.12, Vitamin C, Vitamin E, coenzyme Q, carotene, or glutathione, in sufficient amount to enhance the prophylactic effect.

21. A method according to claim 1, wherein said dose is administered as a tablet, capsule, or powder.

22. A method according to claim 1, wherein said dose is administered as a prepared solid food or liquid.

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Patent History
Patent number: 5891459
Type: Grant
Filed: Nov 9, 1995
Date of Patent: Apr 6, 1999
Assignee: The Board of Trustees of the Leland Stanford Junior University (Stanford, CA)
Inventors: John P. Cooke (Palo Alto, CA), Victor J. Dzau (Los Altos Hills, CA), Gary H. Gibbons (Palo Alto, CA)
Primary Examiner: Jeffrey E. Russel
Attorney: Bertram I. Flehr Hohbach Test Albritton & Herbert Rowland
Application Number: 8/556,035